Cancer can arise from infection of a virus or when there is a change in the DNA code in a region that controls the cell cycle. In the cell cycle, there are proteins (coded for by the DNA) which regulate how often the cell undergoes a division, and also sets up checkpoints to fix cell damage if detected. One of these proteins related to the cell cycle is p53, discovered by Professor Sir David Lane and Lionel Crawford in 1979. The gene that encodes p53 was later discovered in 1989 and is now considered the “guardian of the genome”, as a tumour suppressor.
The process of Lane and Crawford’s discovery began when they were investigating simian virus 40 (SV40), a virus which causes cancer in mice. They noticed a viral protein they analysed was heavier than expected and with further experiments discovered that there was another protein attached. The protein had a weight of 53 kiloDaltons, giving it the name of p53. They figured this protein was too large to be coded from the virus’ DNA so they concluded the protein originated from the mouse cell itself.
In healthy cells, p53 proteins are very low in concentration. It can act as a transcription factor, a protein that regulates the expression of other genes. p53 is then degraded, hence its low concentration. When a cell undergoes stress however, the degradation of p53 is prevented. Consequently, p53 increases and the cell will either go into cell cycle arrest or undergo cell suicide. In cell cycle arrest, damage to the DNA is detected and the cycle is halted until this damage has been fixed. Cell suicide (called apopstasis) is seen as the last resort, to prevent damaged DNA being transferred to the daughter cells of the division.
A visible example of cell suicide being activated as a result of stress or damage is sunburnt skin. The peeling of the skin is a result of cells undergoing suicide from damage done by UV rays, in attempt to prevent skin cancer. As long as the p53 gene is intact, it is an ingenious mechanism evolution has given us to protect us from cancer.
Despite this, things don’t always go to plan. Mutations in the p53 gene can occur, forming mutant forms of the p53 proteins; in fact, at least 50% of human tumours have a mutant form of p53. The significance of the protein has made it a highly active research field – the possibility of reactivating a mutant p53 gene, therefore restoring the p53 functions specifically in tumour cells could possibly stop the growth of tumours and even cause it to reduce in size. On the other hand, tightly regulating p53 in healthy cells during a course of chemotherapy, gives rise to the possibility of saving normal cells from getting damaged.We have also recently discovered the presence of p53 variants, called isoforms. The role of each of these isoforms in protein function is yet to be fully understood alongside the p53 pathway itself. There is still a lot to be discovered when it comes to this guardian of the genome, its interactions with many other proteins and genes alike means there’s no simple description or explanation of its role.